1.results from receptor stimulation due to irritation, distension or stretching
2.pharyngeal afferent (CN 9)
3.sympathetic and vagal afferents (CN 10). acetylcholine is major neurotransmitter. receptors are found in the heart or great vessels and abdominal organs and peritoneum

peripherally acting emetics

1.salt solution
2.3% hydrogen peroxide
3.ipecac syrup: contains an alkaloid emetine which works both through peripheral and central (CRTZ) stimulation

central acting emetics

1.apomorphine:stimulates dopaminergric receptors in the CRTZ. cats are not responsive to apomorphine
2.xylazine (rompun):alpha adenergic agonist drug generally used for sedation but also has emetic in cats, less so in dogs

antiemetics which act at the vestibular apparatus

1.antihistamines
2.scopolamine (belladonna alkaloids)

CRTZ antiemetics

1.phenothiazine:tranquilizers when given at low dose have a central antiemtic action). cosidered to be a broad spectrum antiemetic with actions at both CRTZ and vomiting center. Antihistaminergic effects. antidopaminergic effects. caution can cause alpha adenergic blockage and peripheral hypotension. may lower seizure threshold
2.Metoclopramide:anitdopaminergic effects
3.glucocorticoids (dex):unknown action possibly being synergic with other antiemetics
4.serotonin (5HT3) antagonists: used to block chemotherapy induced vomiting, ondansetron, delansetron, cyproheptadine

central antiemetics

1.phenobarbital
2.benzodiazepines (valium)

peripheral acitng antiemetics

1.anticholinergic drugs:block muscarinic receptors or peripherial cholinergic transmission to the vomiting center (vagal afferents). will also inhibit GI motility and secretion and thus may be contraindicated in some situations
2.protectants and prokinetics

1.cimetidine will inhibit hepatic cytochrome P450 enzymes and can alter hepatic metabolism of other drugs
2.they have variable effect in preventing ulceration but rapidly promote healing of ulcers
3.have partial renal excretion and in renal failure dosage should be reduced (possibly as high as 50% original dose)

irreversible antagonists of the enzyme H+, K+ ATPase at the proton pump which is the final step in gastric acid secretion
1.greater potency than the H2 receptor antagonists
2.may alter hepatic metabolism of other drugs via cytochrome P450 enzymes
3.indicated when the H2 receptor blockers fail to reduce acid production

1. the vomiting patient
2. may absorb other drugs
3. may cause constipation

sucralfate

a sucrose aluminum hydroxide compound that binds to and protects the ulcer form damage thus acting like a surface band aid
Actions
1.surcose compound binds to damaged anions of GI epithelial membranes
2.inactivates acid, bile acids, and pepsin
3.stimulates formation of local prostaglandins
4.stimulates epidermal growth factors and may be a free radical scavenger
5.increases local mucosal blood flow.
will bind other drugs. if used with H2 receptor antagonists dosing bt drugs should be separated by several hours. also has protection for esophagitis, enteritis and colitis

Uses:
acute nonspecific diarrhea. main benefit of agents is related to ability to reduce intestinal secretions
drug examples:
1.atropine
2.aminopentamide
side effects:
1.dry mouth, urinary retention, constipation
2.do not use with invasive bacterial diarrheas
3.do not use longer than 3 days- prolonged use can result in marked GI hypomotility

opioids in diarrhea treatment

most common drug classification used for nonspecific diarrhea
actions:
1.increases segmentations of small instestine
2.decreases propulsive contractions (net effect is increased resistance to flow through GI tract)
3.increased fluid and water absorption
opoid drugs:
diphenoxylate
loperamide
sepcific facts:
1.diphenoxylate is a regulated narcotic
2.loperamide does not cross blood brain barrier and is not regulated and is available as an OTC drug
uses:
acute nonspecific diarrhea

1.are salts or compounds that retain or attract water into the lumen via osmotic forces
2. agents are contraindiacated in the dehydrated patient
3.examples:
magnesium sulfate
sodium phsophates
lactulose

lactulose

osmotic cathartic
fermented by bacteria in the colon producing organic acids.
is used to treat hepatic encephalopathy: traps ammonia in colon preventing absorption. colonic acids produced from lactulose convert NH3 to NH4 that is poorly absorbed

1.warm water
2.hypertonic saline solutions
3.phosphate containing solutions
a.phosphate salts will pull fluid and electorlytes into the colon
b.do not use in cats or debilitated animals
c.results in hyperphosphatemia, hypocalcemia and hypernatremia in cats that is often fatal

1.drugs that prevent formation of collagen or promote their removal from an organ
2.cirrhosis or other fibrosing liver diseases are often treated with antifibrotic agents
3.drugs:
colchicine
anit inflammatory agents also have antifibrotic effects because inflammation is the factor stimulates collagen deposition

a biological phenomenon and is the state that develops as a result of the adaptation (tolerance) produced by repeated drug administration and is produced by the resetting of homeostatic mechanisms. a patient in this altered state requires continued administration of the drug to maintain normal function

any chemical substance naturallly formed in the body that exhibits pharmacological properties of morphine

endorphin

opiate receptors

Mu, delta, kappa currently reffered to as MOP DOP and KOP. a fourth opioid peptide receptor termed nociceptin/orphanin FQ was coloned in 1994. It appears to play impotant roles in the hippocampus, cortex and numerous sensory sites and have effects on drug reward and reinforcement, stress responsiveness, learning and memory processes

pro opiomelanocortin- derived peptides

beta endorphin; the most potent of the natural opioids. Is a precursor for ACTH and melanocyte stimulating hormone. distributed primarily in the anterior and intermediate lobes of the pituitary gland. Modulating/hormonal effect on the CNS. stimulates mu receptors primarily and delta receptors to a lesser extent. mediates analgesia

pro enkephalin derived peptides

met-enkephalin and Leu-enkephalin. widely distributed throughout the CNS.
have a short acting, neurotransmitter function and stimulate delta receptors and mediate analgesia

CNS areas related to the perception of pain

laminae I and II of the spinal cord.
spinal trigeminal nucleus
periaqueductal gray

binding of opioids to receptors stimulates a cascade of intracellular events, leading to

the hyperpolariztion of cell membranes, decrease in nociceptive neurotransmitter release, and inhibition of the nociceptive pathways

affinity

a drug's ability to bind to its receptor sites in the body. for example, buprenophine has a high affinity for mu-opiate recetors and is difficult to antagonize with an opioid antagonist such as naloxone

opioid potency

is directly related to the affinity of the drug for opiate receptor sites. clinically, potency is used to determine the dose of a given opioid, but does not indicate the ability of the drug to provide analgesia

how do opioids cause respiratory depression

rerduction in the responsiveness of the brainstem respiratory centers to carbon dioxide, and opioids depress the pontine and meduallary centers involved in regulating respiratory rhythmicity

do opioids cause miosis or mydriasis

they casue miosis in the dog, rabbit, rat, and human. cause mydriasis in the monkey, cat, sheep, and horse

T/F opioids are not contraindicated in animals with a history of seizures

T. opioids may cause convulsions at excessively high doses (overdose). Morphine like drugs excite hippocampal cells, possibly due to inhibition of GABA by inhibitory interneurons

opioids and vasodilation

vasodilation is generally a result of morphine or meperidine induced histamine release. Histamine release can occur with hdromorphone, but clinically appears to be minimal. vasodilation may also occur as a result of pain relieve and withdrawal of sympathetic tone

why would you consider avoiding morphine in dogs with pancreatitis

in dogs morphine can induce contraction of the sphincter of Oddi, resulting in an inhibition of pancreatic secretions and abdominal pain

What speices of animal is the constipating effects of morphine a serious concern

horses

epidural morphine in dogs and cats may cause retention of urine for a period of __________

24 hours or more

which type of opioids should not be used during sedation/anesthesia for skin allergy testing.

ones that have histamine releasing effects:
morphine, meperidine

tramadol

is a syntheically derived analgesic that possesses weak mu-opioid activity and inhibits norepineprine and serotonin re-uptake. Not a controlled drug

phenothiazines

tranquilizers
examples;
acepromazine
chlorpromazine
promazine

what is the significance of hepatic metabolism and urinary excretion of phenothiazines

aged individuals and those with liver disease may have a prolonged duration of effect

The calming effects of phenothiazines are enhanced with the concurrent administration of

opioids or alpha 2 agonists

do phenothiazines provide analgesia

No, but are givin freuently in combination with opioids to provide analgesia

phenothiazines

tranquilizers
examples:
acepromazine
chlorpromazine
promazine

What is the significance of hepatic metabolism and urinary excretion or phenothiazines

aged indivdiuals and those with liver disease may have a prolonged duration of effect

The calming effects of phenothiazines are enhanced with the concurrent administration of

opioids or alpha 2 agonsits

Do pheonthiazines have an analgesic effect

No, but are frequently administered in combination with opioids to provide analgesia

decreased motor activity of phenothiazines is assoicated with ataxia in horses givin ________ but not _________

Why do you avoid use of phenothiazines when skin testing for allergies

they have an anti-histaminic effect

what side effect can phenothiazines produce in the eye

nictitating membrane prolapse

Why are phenothiazines sometimes avoided in stallions

may cause erection and temporary or permanent prolapse of the penis

phenothaizines inhibit the function of what type of cells in the blood

platelets

butyrophenones

similar to phenothiazines
minimal use in veterinary medicine

alhpa 2 agonists mechanism of action

stimulation of presynaptic alpha 2 adrenoceptors (G-protein linked receptors). Stimulation of central alpha 2 adrenoceptors decreases the release of norepinephrine decreased syaptheric outflow. alpha 2 adrenoceptors subtypes may play a role in specific effects observed with various alpha 2 agonists. stimulation of alpha 1 adrenoceptors (central and peripheral). central parasympathomimetic effect. Muscle relaxation- inhibition of interneuronal transmission of impulses in the CNS. local anesthetic effect- xylazine as a membrane stabilizing effect which is most evident when xylazine is administered via the epidural route. This effect is not as profound as with local anesthetic drugs.

alpha 2 antagonist
60x more selective for a2 than a1
enhances release of excitatory neurotransmitters (norepinephrine)
may induce anxiety, pacing, and panting in dogs, rough recoveries in aany species

tolazoline

alpha 2 antagonist
least specific of a2 antagonsits
-in osme cases, may be more effective and provide a smoother recovery form xylazine than yohimbine
potent H2 receptor agonsit- the significance of this effect in veterinary species is unclear
immediate and delayed deaths have occurred in llamas administered tolazoline

atipamezole

alpha 2 antagonist
most specific and most effective a2 antagonist
no appreciable effects at other receptors